Interrelated and integrated studies Of Subjects with periodontal diseases or in periodontal health will be carried out, as will in vitro studies of the immunopathogenesis of periodontal diseases. The goals of the proposed studies are to improve knowledge of factors contributing to the etiology and pathogenesis of periodontal diseases. The human subjects for most of the proposed studies will be identified within the framework of our efforts to define genetic influences on periodontal diseases. These subjects will be initially screened and clinically characterized by investigators in the Core section of the Program Project, and appropriate clinical samples and other pertinent information will be collected. Since our previouS data indicate that the expression of early onset periodontitis (juvenile periodontitis [JP] and severe periodontitis [SP]) could be genetically determined, we will continue to test genetic hypotheses of the mode of transmission of these diseases, and will begin linkage analyses to attempt to map genes that influence these diseases to their chromosomal locations. In addition, we will begin a study to determine whether there is a genetic influence on other (adult) forms of periodontitis or periodontal health by studying disease characteristics of adult monozygous (MZ) and dizygous (DZ) twin pairs. Using cultural studies of the subgingival flora of healthy and diseased pairs of MZ and DZ twins, we will examine the influence of genes vs. environment on the subgingival bacterial flora. Analyses of these data will provide information about the etiology of periodontal disease and about bacterial ecology. Studies of the immune response to organisms characteristic of the disease category of the twin pair members will be carried out to determine the influence of genes upon the immune response to oral bacteria, and further studies of genetic influences on the antibody response to periodontal organisms in JP-SP families are proposed. In addition, we will further study non-specific immune and inflammatory responses as immunopathogenic mechanisms in periodontal diseases. Finally, studies in which the course of disease in JP-SP families will be monitored and correlated to their immune status and the presence of bacterial pathogens will be carried out.